Serinol → 3-(1,3-dihydroxypropan-2-yl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 1660902Notes

Reaction equation

[N+](C1C=C([N+]([O-])=O)C=CC=1N1[C:18](=[O:19])[C:17]2[C:20]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=3[F:34])=[CH:21][C:22](=[O:25])[N:23]([CH3:24])[C:16]=2[N:15]=[CH:14]1)([O-])=O.[NH2:35][CH:36]([CH2:39][OH:40])[CH2:37][OH:38]>CN(C=O)C>[OH:38][CH2:37][CH:36]([N:35]1[C:18](=[O:19])[C:17]2[C:20]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=3[F:34])=[CH:21][C:22](=[O:25])[N:23]([CH3:24])[C:16]=2[N:15]=[CH:14]1)[CH2:39][OH:40]

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of 3-(2,4-dinitrophenyl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione 24A (18 mg, 0.03 mmol, 1 eq) in DMF (0.3 mL) was added 2-aminopropane-1,3-diol (29 mg, 0.3 mmol, 10 eq). The reaction mixture was heated at 80° C. for 5 hours. The solvent was removed under vacuum and the residue was purified by preparatory LC/MS (30-55% CH3CN in H2O) to yield 3-(1,3-dihydroxypropan-2-yl)-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione Example 24 as an off-white solid (10 mg, 66% yield). 1H NMR (400 MHz, MeOD) δ ppm 3.65 (s, 3H) 3.87-3.95 (m, 2H) 4.04 (dd, J=11.87, 7.07 Hz, 2H) 4.88-4.90 (m, 1H) 5.74 (s, 1H) 7.29 (t, J=8.34 Hz, 1H) 7.57-7.69 (m, 2H) 8.50 (s, 1H). [M+H] calc'd for C17H16FIN4O4, 487; found, 487.

Workup

customThe solvent was removed under vacuum
customthe residue was purified by preparatory LC/MS (30-55% CH3CN in H2O)

Sources & evidence

ORD record: ord-48e9f9b8df4048389b8854211c5c2268
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030317B2

Reaction notes

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